No abstract

No abstract

No abstract

The latest advances in the catalytic synthesis of biologically active compounds with 2-amino-3,5-dicarbonitrile-6-sulfanylpyridine scaffold via the multicomponent reactions of malononitrile have been discussed.

Twelve new α,ω-bis[(3,5-dimethylpyrazol-4-yl)methylsulfanyl]alkanes linked by alkyl, diethyl sulfide, and triethyl dioxide spacers were prepared by the multicomponent reaction of acetylacetone, formaldehyde, α,ω-dithiols, and monosubstituted hydrazines. Testing of these products for inhibition of α-amylase enzyme in vitro showed that bis(N-methylpyrazolylmethylsulfanyl)ethane 4a inhibits the enzyme by the competitive mechanism. Meanwhile, the water-soluble adduct of bis(isoxazolylmethylsulfanyl)ethane 2 with HCl (2·HCl) is a noncompetitive inhibitor. The molecular docking results attest to high complementarity between the test molecules and the enzymes such as α-amylases from Aspergillus niger and human pancreas. Bis-pyrazole compounds 1, 1·HCl, and 4a and bis-isoxazole compounds 2 and 2·HCl positioned in the active site of both α-amylases form two closely spaced clusters. For all cases, the bioactive conformations of the modeled ligands were identified, demonstrating high affinity of the bis-azoles (1, 1·HCl, 2, 2·HCl, 4a) to the enzymes. Hydrogen bonds stabilizing their position in both α-amylases active sites were identified.